The traditional manner of using a medication to achieve an effect on an internal condition has been to use the non-invasive routes of oral, rectal, and nasal administration, and invasive routes of intravenous, subcutaneous and intramuscular administration. All of these routes depend on the medication entering the bloodstream, reaching effective levels and then exerting its effects on the internal organ or site. The medication could be introduced at any of the available sites in relation to the internal organ--there is no requirement of a specific site of application of the medication.
The cutaneous route of administration has also been used. All known cutaneous applications of medication to achieve their desired effects have been by one of two general mechanisms. One mechanism is the direct absorption of medication into the area of pathology to achieve a desired local effect. That is, the medication is placed directly over the site where it is expected to act. The medicine then absorbs through the skin to the site. Examples include the use of topical steroids (eg, the use of triamcinolone to treat eczema), and the use of topical capsaicin for the treatment of post-herpetic neuralgia. In this method, it makes no sense or utility to place capsaicin on the left arm when the Herpes zoster is on the right arm--the medicine must be placed directly on the site it is to effect. The other accepted mechanism is to use the skin as a means of delivering medication to the systemic circulation. The medication is absorbed through the skin and into the blood stream. The circulatory system then delivers the medicine to the site of pathology. Examples of that mechanism include the use of nitroglycerin ointment to treat angina pectoris of the heart, estrogen patches which act on the uterus and catapres patches for blood pressure control which act on the brain. The site of medication application to the skin is generally independent of the target site of action. That is, the medication may be placed, more or less, randomly on the skin. Another requirement is that the topical medication must be placed on the skin in large enough amounts to be absorbed into the blood stream and reach therapeutic levels. This is accomplished by higher concentrations of the medication in a reservoir, by the use of agents which enhance the absorption of medication present, and by delivery devices which control the rate of absorption such that overdose or dumping of the medicine does not occur. So, for a topical nitroglycerin patch to treat angina of the heart, an internal organ, the patch does not have to be placed over the heart. In fact the patch can be placed anywhere on the skin, no specific site is required. The only goal is to have as much of the medication as possible absorb through the skin and reach therapeutic blood levels at the heart.
The method of the present invention is distinctly different from all of the above methods and specifically different from the traditional methods of use of topical medications. None of the methods above require a specific site of application, or injection, to treat an internal organ condition. Our method requires a specific site of application to treat a distant internal organ. Whereas all of the above conditions require a systemic blood level to achieve its effect on an internal organ, our method does not require blood levels and, in fact, uses dosages of capsaicin which are far less than those used for systemic effects. Whereas our method requires specific topical application of capsaicin for effectiveness, that application is not directly on the site of its intended effect and is not directly on the site of pathology. All of these differences show the uniqueness of this invention.
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the pungent principle of red peppers, has been used cutaneously for the treatment of pain. Synthetic capsaicin (nonyl vanillylamide) acts in the same manner as capsaicin, and capsaicin (more properly capsaicinoids) is meant to include this substance for brevity. Capsaicin is believed to act on a subset of primary afferent nerves mostly of the C fiber type (polymodal, thin, unmyelinated), although some A delta (thin, myelinated) are also capsaicin sensitive. Capsaicin is believed to bind to a receptor at the nerve ending and cause a release of a variety of neuropeptides (e.g., substance P,CGRP and others) and results in afferent nerve conduction initially. There are two main phases of action, first an excitation and then a desensitization of the nerve to stimulation. The excitation results in the `hot` of hot pepper or the burning tingling sensation which can occur when capsaicin is applied to the skin. The desensitization results from the depletion of neuropeptides and interference with afferent conduction in a non-tetrodotoxin dependent manner. It has been demonstrated that topically (skin) applied capsaicin can deplete neuropeptides at the peripheral (cutaneous) and central (dorsal horn of spinal cord) endings of the peripheral cutaneous nerve. To date patents and articles have only described the use of capsaicin to treat cutaneous conditions (e.g., psoriasis or post-herpetic neuralgia), neuropathic conditions affecting the skin or subcutaneous area (e.g., postmastectomy neuroma or diabetic neuropathy) or direct subcutaneous conditions (e.g., osteoarthritis or rheumatoid arthritis). All of these treatments use the cutaneous application of the capsaicin to affect direct subcutaneous pathology (i.e., the local effect). These methods require direct application at the site of pathology (i.e., no internal conditions).
It is believed that no method of treatment has been described in the literature which employs the isolated topical application of capsaicin to the skin to achieve systemic effects for an internal condition distant from the site of application. Furthermore, no literature or available medicine was found which describes the treatment of an internal condition by topical application of that medication which did not require systemic absorption of the medication. Capsaicin has only been applied directly over the site of pathology for its therapeutic uses. The application of a medication at a specific skin site in amounts that cannot achieve significant systemic blood levels to treat a distant internal site of pathology has not been done--this invention is truly unique and unexpected.